Co‐delivery of Doxorubicin and Bcl‐2 siRNA by Mesoporous Silica Nanoparticles Enhances the Efficacy of Chemotherapy in Multidrug‐Resistant Cancer Cells

Chen, Alex M.; Zhang, Min; Wei, Dongguang; Stueber, Dirk; Taratula, Oleh; Minko, Tamara; He, Huixin

doi:10.1002/smll.200900621

Cited by 611 publications

(450 citation statements)

References 39 publications

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“…Currently, epidermal growth factor receptor-targeted polymeric nanoparticles that actively target MDR-associated phenotypes have been reported and several targeted nanoparticles have been investigated in preclinical studies for cancers [30,50]. Furthermore, the development of combination therapies that inhibit MDR and deliver cytotoxic drugs has been recently investigated [8,29,38]. Liposome-based nanoparticles can be used as effective codelivery vehicles for Dox and siRNA and cause the simultaneous suppression of drug efflux pumps and antiapoptotic cellular defense combined with cell death induction [38].…”

Section: Discussionmentioning

confidence: 99%

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

Kobayashi

Iyer

Hornicek

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background The toxicity of anticancer agents and the difficulty in delivering drugs selectively to tumor cells pose a challenge in overcoming multidrug resistance (MDR). Recently, nanotechnology has emerged as a powerful tool in addressing some of the barriers to drug delivery, including MDR in cancer, by utilizing alternate routes of cellular entry and targeted delivery of drugs and genes. However, it is unclear whether doxorubicin (Dox) can be delivered by nanotechnologic approaches. Questions/Purposes We asked whether (1) Dox-loaded lipidfunctionalized dextran-based biocompatible nanoparticles (Dox/NP) can reverse MDR, (2) Dox/NP has more potent cytotoxic effect on MDR tumors than poly(ethylene glycol)-modified liposomal Dox (PLD), and (3) multidrug resistance protein 1 (MDR1) small interfering RNA loaded in these nanoparticles (siMDR1/NP) can modulate MDR. Methods To create stable Dox/NP and siMDR1/NP, we used two different lipid-modified dextran derivatives. The effect of Dox or Dox/NP was tested on drug-sensitive osteosarcoma (KHOS) and ovarian cancer (SKOV-3) cell cultures in triplicate and their respective MDR counterparts KHOS R2 and SKOV-3 TR in triplicate. We determined the effects on drug retention, transfection efficacy of siMDR1/ NP, and P-glycoprotein expression and the antiproliferative effect between Dox/NP and PLD in MDR tumor cells. Results Fluorescence microscopy revealed efficient uptake of the Dox/NP and fluorescently tagged siMDR1/ NP. Dox/NP showed five-to 10-fold higher antiproliferative activity at the 50% inhibitory concentration than free Dox in tumor cells. Dox/NP showed twofold higher activity than PLD in MDR tumor cells. siMDR1/NP (100 nM) suppressed P-glycoprotein expression in KHOS R2 . Conclusions Dextran-lipid nanoparticles are a promising platform for delivering Dox and siRNAs. Clinical Relevance Biocompatible dextran-based nanoparticles that are directly translatable to clinical medicine

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Section: Discussionmentioning

confidence: 99%

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

Kobayashi

Iyer

Hornicek

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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“…On the first contribution aimed at cancer treatment, Chen et al employed the developed transfection strategy which used a 2 nd generation PAMAM dendrimer to deliver the Bcl-2 antiapoptotic siRNA; although in this case DOX was loaded into the mesopores. 157 The combined effect of both agents showed a 132-fold increased apoptosis in comparison to free DOX, obtained by the suppression of the Bcl-2 mediated resistance on A2780/AD human ovarian cancer cells (Entry 1, Table 2). Employing a similar strategy Zhao et al reported a design which employed PEI as linking material between MSNs and siRNA; moreover, in this case folic acid was incorporated as active targeting.…”

Section: Please Do Not Adjust Marginsmentioning

confidence: 99%

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

Castillo¹,

Baeza²

2017

Biomater. Sci.

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The discovery and control of the biological roles mediated by nucleic acids have turned them into a powerful tool for the development of advanced biotechnological materials. Much is the importance of those gene-keeping biomacromolecules that even nanomaterials have succumbed to the claimed benefits of DNA and RNA. Currently, there could be found in the literature a practically intractable number of examples which report the use in combination of nanoparticles with nucleic acids, which demands boundedness. Following this premise, this revision will only cover the most recent and powerful strategies developed to exploit the possibilities of nucleic acids as biotechnological materials when in combination with mesoporous silica nanoparticles. The extensive research done on nucleic acids has significantly incremented the technological possibilities for those biomacromolecules, which could be employed in many different applications; where substrate or sequence recognition or modulation of biological pathways due to its coding role in living cells are the most promising. In the present revision, the chosen counterpart, mesoporous silica nanoparticles, also with unique properties, became a reference material for drug delivery and biomedical applications due to their high biocompatibility and porous structure suitable for hosting and delivering small molecules. Although most of revisions deal with significant advances in the use of nucleic acid and mesoporous silica nanoparticles in biotechnological applications, a rationale classification of those new generation hybrid materials is still uncovered. Along this review there will be covered promising strategies for living cell and biological sensors, DNA-based molecular gates with targeting, transfection or silencing properties which could provide a significant advance of current nanomedicine.

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“…Several antibodies targeting Notch signalling as well as γ-secretase inhibitors are currently in stage II of clinical trials [114]. Other signalling pathways that are known to regulate cancer stem cells include JAK/ STAT, Wnt, hedgehog, Bcl-2, NF-ĸB and others [115][116][117][118][119]. These various signalling molecules can be targeted by small molecule inhibitors to eliminate CSC homeostasis.…”

Section: Cscs and Microenvironmentmentioning

confidence: 99%

Cancer Stem Cells: Formidable Allies of Cancer

Deshpande

Rangarajan

2015

Indian J Surg Oncol

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Cancer stem cells (CSC) represent the subpopulation of cells within a tumour showing two fundamental properties of stem cells -self-renewal (the ability to make more of their own kind) and differentiation (the ability to generate diverse cell types present within a tissue). The CSC hypothesis posits that CSCs play an important role in tumour initiation, maintenance and progression. Furthermore, owing to their intrinsic drug resistance, they remain refractory to currently used therapy, thereby contributing to tumour relapse. Thus, targeting or taming CSCs can lead to more effective cancer treatment in the coming decades. In this review, we will discuss about the origin of CSC hypothesis, evidence showing their existence, clinical relevance and translational significance.

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Co‐delivery of Doxorubicin and Bcl‐2 siRNA by Mesoporous Silica Nanoparticles Enhances the Efficacy of Chemotherapy in Multidrug‐Resistant Cancer Cells

Cited by 611 publications

References 39 publications

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

Cancer Stem Cells: Formidable Allies of Cancer

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